Evaluating the metabolic, production, and inflammatory consequences of hindgut acidosis in dairy cows

Abstract

In the past several decades, major advancements have been made in individual dairy cow productivity and this can largely be attributed to expansions in our understanding of genetics, the incorporation of precision technologies on the farm, and the great importance of nutrient partitioning in fully taking advantage of a cow’s genetic capacity for milk production. Immune activation initiates a cascade of homeorhetic adjustments to siphon nutrients (glucose) away from productive purposes (milk synthesis) and towards fueling immune functions. There are several potential sources of inflammation in dairy cows including direct infection of the mammary gland, uterus, or lungs, and several stress insults (i.e., heat stress, feed restriction, etc.) can compromise intestinal barrier integrity leading to an immune response. Additionally, high grain feeding can cause intestinal barrier dysfunction when rumen acidosis develops; yet, despite the importance of immune activation in impeding optimal performance, the etiological mechanisms by which rumen acidosis disrupts intestinal barrier integrity remains incompletely characterized. Generally, acute or prolonged rumen acidosis has obvious consequences to the barrier of the entire alimentary canal including sloughing of epithelia, hyperkeratinization, and severe barrier dysfunction. However, during mild- to moderate sub-acute rumen acidosis (SARA), it is unclear which site(s) inflammation stems from. This is particularly because relative to the rumen, the small and large intestine epitheliums are seemingly ill-equipped to handle the noxious environment created by excessive fermentation (i.e., low pH, increased endotoxin, ethanol, etc.). During rumen acidosis the quantity of starch reaching the large intestine increases and results in an elevation of hindgut fermentation. There is evidence in the monogastric literature suggesting that the large intestine barrier can become compromised during hindgut acidosis. However, inconsistencies have been reported in dairy cows indicating a need for better characterization of how hindgut acidosis impacts intestinal barrier integrity. In this dissertation, we have thoroughly evaluated the effects of moderate hindgut acidosis on production, metabolism, and inflammation in dairy cows, and the accumulation of results from the chapters herein suggest that isolated moderate hindgut acidosis does not affect large intestine barrier integrity. Further, during SARA, fecal pH depressions associated with increased hindgut fermentation are comparable to if not more mild than those observed in our isolated hindgut acidosis experiments. Therefore, these results indicate that pathology associated with increased hindgut fermentation is not the etiological impetus of SARA induced inflammation. However, evidence from chapter 6 suggests that future work is warranted investigating the impacts of acute hindgut acidosis on barrier integrity, as there appears to be a link between lactic acid accumulation and intestinal barrier dysfunction in monogastric literature. In summary, intestinal barrier dysfunction remains an important topic within the dairy industry to optimize dairy cow productivity and well-being. However, hindgut acidosis during SARA is likely not an etiological contributor towards immune activation, and thus, future efforts should expand on characterizing whether lactic acid constitutes the tipping point at which excessive fermentation becomes detrimental to barrier integrity.